To date, the use of marketed continuous glucose monitoring systems (CGMs) are limited to glucose trend analysis by patients with insulin-dependent type 1 and type 2 diabetes. Accuracy limitations, particularly in the hypoglycemic range, and low signal-to-noise ratio have precluded expansion of this promising technology into screening applications to identify early signs of diabetes, prior to clinical onset of disease, so preventive measures may be taken. The proposed research is focused on developing an in vitro model of glycemic oscillations in yeast using a combined yeast-biosensor hybrid. The information derived from this model will be used to determine if manifestations of glycemic oscillations can be measured and characterized within the interstitial fluid (ISF) of humans. So far, the phenomenon of in vivo interstitial fluid glycemic oscillations has not been reported. Preliminary in vivo interstitial fluid glucose data, measured in the dermis of swine, revealed an oscillatory phenomenon that may be indicative of intracellular glycolysis. Included in the Specific Aims is the development of an in vitro yeast-biosensor hybrid system that models the in vivo ISF environment. This unique hybrid, continuous glucose monitoring system will be used to develop a model of glycemic oscillations in yeast. Data from the in vitro model will be used to develop pattern recognition algorithms to characterize in vivo ISF oscillations specific to type 1 and type 2 diabetes. Successful completion of the proposed research will provide advances in continuous glucose monitoring technology that have the potential to resolve inaccuracy issues encountered by patients using CGMs. It is our belief the proposed research will break-down technical barriers that preclude the use of this technology as a stand-alone system with expanded utility for screening and preventative applications that may bring the artificial pancreas on step closer to reality. PUBLIC HEALTH RELEVANCE: The potential for continuous glucose monitoring systems (CGMs) to detect glycemic oscillations in interstitial fluid will advance the use of this technology into the realm of preventative medicine by providing an inexpensive screening tool, capable of identifying people with abnormal glucose metabolism long before overt clinical symptoms are apparent. The outcomes of the proposed research will allow physicians to intervene early in the progression of diabetes symptoms with low cost diet and lifestyle changes as opposed to high cost therapeutic intervention. Early stage intervention will have a significant impact on reducing the over $200 billion annual cost to the US healthcare system to treat the chronic complications of diabetes.